TY - JOUR
T1 - Simplification to atazanavir/ritonavir monotherapy for HIV-1 treated individuals on virological suppression
T2 - 48-week efficacy and safety results
AU - MODAt Study Group
AU - Castagna, Antonella
AU - Spagnuolo, Vincenzo
AU - Galli, Laura
AU - Vinci, Concetta
AU - Nozza, Silvia
AU - Carini, Elisabetta
AU - Monforte, Antonella D.Arminio
AU - Montella, Francesco
AU - Antinori, Andrea
AU - Di Biagio, Antonio
AU - Rusconi, Stefano
AU - Lazzarin, Adriano
AU - Viscoli, C.
AU - Parisini, A.
AU - Prinapori, R.
AU - Mazzotta, F.
AU - Lo Caputo, S.
AU - Di Pietro, M.
AU - D'Arminio-Monforte, A.
AU - Tincati, C.
AU - Bini, T.
AU - Merlini, E.
AU - Puoti, M.
AU - Moioli, M.
AU - Montella, M.
AU - Di Sora, F.
AU - Ammassari, A.
AU - Ottou, S.
AU - Cauda, R.
AU - Di Giambenedetto, S.
AU - Galli, Massimo
AU - Franzetti, M.
AU - Rizzardini, G.
AU - Capetti, A.
AU - Cossarini, F.
AU - Gianotti, N.
AU - Mussini, C.
AU - Guaraldi, G.
N1 - Publisher Copyright:
© 2014 Wolters Kluwer Health-Lippincott Williams & Wilkins.
PY - 2014
Y1 - 2014
N2 - Objectives: The objective of this study was to assess the 48-week virological efficacy of atazanavir/ritonavir (ATV/r) monotherapy vs. ATV/r along with two nucleoside reverse transcriptase (NRTIs) in HIV-1 treated individuals with HIV-RNA less than 50 copies/ml. Methods: A multicentre, randomized, open-label, noninferiority trial. HIV-1 treated individuals on ATV/r 300/100mg along with two NRTIs were randomized to receive ATV/r monotherapy or to maintain their antiretroviral regimen. The primary endpoint was the confirmed viral rebound (CVR: Two consecutive HIV-RNA >50 copies/ml) or treatment discontinuation for any reason. Individuals who experienced CVR on ATV/r monotherapy reintroduced NRTIs and discontinued the study if HIV-RNA was more than 50 copies/ml after 12 weeks since reintensification. Results: One hundred and three patients enrolled. By week 48, 11 patients in ATV/r arm and two in ATV/r along with twoNRTIs experienced CVR; four (8%) patients in ATV/r and eight (15%) in ATV/r along with twoNRTIs discontinued. At the 48-week primary efficacy analysis (re-intensification=failure), treatment success was73%inATV/r armand85%in ATV/r along with two NRTIs [difference 12.1%, 95% confidence interval (95% CI)27.8 to 2.1]. According to the analysis considering re-intensification is equal to success, treatment success was 92%in ATV/r armand 85%in the ATV/r along with twoNRTIs arm (difference 7.5%, 95%CI4.7 to 19.8). At CVR, no mutation was observed in ATV/r arm and reintensification with NRTIs was effective in all individuals. Overall, Grade 3-4 (P=0.003) and grade 3-4 drug-related (P=0.027) adverse events were less frequent in ATV/r arm. A significant increase in total and low-density lipoprotein (LDL)-cholesterol was observed as well as a significant improvement in high-density lipoprotein (HDL)- cholesterol, fasting glucose, liver fibrosis and alkaline phosphatase was observed in ATV/r monotherapy in comparison with ATV/r along with two NRTIs. Conclusion: ATV/r monotherapy treatment simplification showed lower virological efficacy in comparison with maintaining triple therapy; NRTIs reintroduction was effective in all the individuals.
AB - Objectives: The objective of this study was to assess the 48-week virological efficacy of atazanavir/ritonavir (ATV/r) monotherapy vs. ATV/r along with two nucleoside reverse transcriptase (NRTIs) in HIV-1 treated individuals with HIV-RNA less than 50 copies/ml. Methods: A multicentre, randomized, open-label, noninferiority trial. HIV-1 treated individuals on ATV/r 300/100mg along with two NRTIs were randomized to receive ATV/r monotherapy or to maintain their antiretroviral regimen. The primary endpoint was the confirmed viral rebound (CVR: Two consecutive HIV-RNA >50 copies/ml) or treatment discontinuation for any reason. Individuals who experienced CVR on ATV/r monotherapy reintroduced NRTIs and discontinued the study if HIV-RNA was more than 50 copies/ml after 12 weeks since reintensification. Results: One hundred and three patients enrolled. By week 48, 11 patients in ATV/r arm and two in ATV/r along with twoNRTIs experienced CVR; four (8%) patients in ATV/r and eight (15%) in ATV/r along with twoNRTIs discontinued. At the 48-week primary efficacy analysis (re-intensification=failure), treatment success was73%inATV/r armand85%in ATV/r along with two NRTIs [difference 12.1%, 95% confidence interval (95% CI)27.8 to 2.1]. According to the analysis considering re-intensification is equal to success, treatment success was 92%in ATV/r armand 85%in the ATV/r along with twoNRTIs arm (difference 7.5%, 95%CI4.7 to 19.8). At CVR, no mutation was observed in ATV/r arm and reintensification with NRTIs was effective in all individuals. Overall, Grade 3-4 (P=0.003) and grade 3-4 drug-related (P=0.027) adverse events were less frequent in ATV/r arm. A significant increase in total and low-density lipoprotein (LDL)-cholesterol was observed as well as a significant improvement in high-density lipoprotein (HDL)- cholesterol, fasting glucose, liver fibrosis and alkaline phosphatase was observed in ATV/r monotherapy in comparison with ATV/r along with two NRTIs. Conclusion: ATV/r monotherapy treatment simplification showed lower virological efficacy in comparison with maintaining triple therapy; NRTIs reintroduction was effective in all the individuals.
KW - Atazanavir/ritonavir
KW - HIV
KW - Nucleos(t)ide reverse transcriptase inhibitors toxicity
KW - Protease inhibitor monotherapy
KW - Simplification
KW - Virological suppression
UR - http://www.scopus.com/inward/record.url?scp=84918843297&partnerID=8YFLogxK
U2 - 10.1097/QAD.0000000000000407
DO - 10.1097/QAD.0000000000000407
M3 - Article
C2 - 25058680
AN - SCOPUS:84918843297
VL - 28
SP - 2269
EP - 2279
JO - AIDS
JF - AIDS
SN - 0269-9370
IS - 15
ER -